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FOXBORO, Mass. — The Patriots have a tremendous track record against rookie quarterbacks during the Bill Belichick era, which doesn’t bode well for Bills starter EJ Manuel.

Manuel’s NFL debut on Sunday will mark the 18th time a rookie quarterback has started against the Patriots since 2000. In 17 previous starts, rookie quarterbacks have bested the Patriots just four times — Ben Roethlisberger (2004), Mark Sanchez (2009), Colt McCoy (2010) and Russell Wilson last season — and none have ever won in their first career start (0-4), making matters even worse for the Bills’ first-round pick.

While history doesn’t offer much of a chance for Manuel and the Bills in the opener, Wilson’s success in the Seahawks’ 24-23 win over the Patriots last season does at least offer some hope.

Wilson had his way with the Patriots’ defense on that rainy October afternoon in Seattle, completing 16 of 27 passes for 293 yards and three touchdowns, including a pair of scores in the final minutes. The killer instinct that Wilson displayed on the Seahawks’ final two drives is something not many players possess, especially as rookies, but the rest of his skill set is very similar to Manuel’s and could cause problems for the Patriots.

Both quarterbacks have notable arm strength and can challenge defenses vertically, which Wilson showed on his clinching 46-yard touchdown pass to Sidney Rice. They are also extremely accurate quarterbacks. Wilson completed 64 percent of his passes as a rookie, finishing eighth league-wide. Meanwhile, albeit in a small sample size, Manuel completed 78 percent (26 for 33) of his passes this preseason. Manuel’s efficiency is no fluke, though. He finished 10th in the nation in completion percentage (68 percent) in 2012 and never completed less than 65 percent of his passes in his four years at Florida State.

The Patriots will face a far greater test with Manuel at quarterback instead of undrafted rookie Jeff Tuel, who was originally expected to start Sunday. Cornerback Kyle Arrington is among those who have already taken note.

“We’ve got a good challenge on our hands,” Arrington said. “We’re just getting prepared and doing as much homework and getting in preparation for their fast-paced offense — spread, read-option. We’re climbing the uphill battle right now.”

Like Wilson, Manuel is also an exceptional athlete. Wilson ran for 489 yards and four touchdowns as a rookie, although he found minimal success against the Patriots — five carries for 17 yards. Manuel enjoyed similar success on the ground last season, rushing for 310 yards and four touchdowns in 14 games as a senior. He could be in a good position to have an even greater impact on the ground against the Patriots, too, especially with C.J. Spiller beside him in the backfield.

“Definitely [he helps],” Manuel said when asked about Spiller’s influence in the backfield. “When you have a guy who can run the ball like C.J., a great guy who has been in this situation before, I know they have my back back there.”

The Patriots will need to be wary of Manuel’s speed and experience carrying the ball, especially in option packages with Spiller. The defense struggled to contain Colin Kaepernick and Frank Gore on their visit to Gillette last season, giving up a season-high 180 rushing yards to the 49ers in what was an uglier loss than the 41-34 final indicates.

The Patriots’ defenders don’t seem to have forgotten about the 49ers’ read-option success, even if they won’t acknowledge it directly. They don’t seem too keen on a repeat performance this season, however, reinforcing the focus to contain Manuel in both facets of the game.

“Whenever you have an athletic guy at the quarterback position [and] they have the scrambling presence, it makes it that much harder,” Arrington said. “Especially when it comes to third down. You’re trying to go up the field, and not only can he throw it, but he can run it for a first down. It can be demoralizing.”

The Patriots haven’t faced much read-option in games this preseason, as Michael Vick didn’t show much, if any, in the Eagles game.Thaddeus Lewis, who happens to be on the Bills’ practice squad now, ran just a handful of them on the Patriots’ visit to Detroit. But the defense does have experience defending the option, practicing against a similar package run by Tim Tebow throughout camp. That’s not to say Tebow could fully prepare the Patriots for Manuel’s skill set, but it’s at least a good point of reference.

With all of the injuries on the Bills’ roster entering Sunday, including the continued uncertainty around safety Jairus Byrd, it’s unlikely Manuel will become the fifth rookie to beat the Patriots. But, if Wilson was any indication, he has a better chance than most might expect.